Profiling of transcripts and proteins modulated by K-ras oncogene in the lung tissues of K-ras transgenic mice by omics approaches.

Abstract

The mutated K-ras gene is involved in approximately 30% of human cancers. In order to search for K-ras oncogene-induced modulators in lung tissues of K-ras transgenic mice, we performed microarray and proteomics (LC/ESI-MS/MS) analysis. Genes (RAB27b RAS family, IL-1RA, IL-33, chemokine ligand 6, epiregulin, EGF-like domain and cathepsin) related to cancer development (Wnt signaling pathway) and inflammation (chemokine/cytokine signaling pathway, Toll receptor signaling) were up-regulated while genes (troponin, tropomodulin 2, endothelial lipase, FGFR4, integrin alpha8 and adenylate cyclase 8) related to the tumor suppression such as p53 pathway, TGF-beta signaling pathway and cadherin signaling pathway were down-regulated by K-ras oncogene. Proteomics approach revealed that up-regulated proteins in lung adenomas of K-ras mice were classified as follows: proteins related to the metabolism/catabolism (increased from 7 to 22% by K-ras gene), proteins related to translation/transcription and nucleotide (from 4 to 6%), proteins related to signal transduction (from 3 to 5%), proteins related to phosphorylation (from 1 to 2%). ATP synthase, Ras oncogene family, cytochrome c oxidase, flavoprotein, TEF 1, adipoprotein A-1 BP, glutathione oxidase, fatty acid BP 4, diaphorase 1, MAPK4 and transgelin were up-regulated by K-ras oncogene. However, integrin alpha1, Ras-interacting protein (Rain), endothelin-converting enzyme-1d and splicing factor 3b were down-regulated. These studies suggest that genes related to cancer development and inflammation were up-regulated while genes related to the tumor suppression were down-regulated by K-ras, resulting in the tumor growth. Putative biomarkers such as cell cycle related genes (Cdc37), cancer cell adhesion (Glycam 1, integrin alpha8, integrin alphaX and Clec4n), signal transduction (Tlr2, IL-33, and Ccbp2), migration (Ccr1, Ccl6, and diaphorase 1 (Cyb5r3) and cancer development (epiregulin) can be useful for diagnosis and as prognosis markers and some of the target molecules can be applied for prevention of cancer.

• Authors: Sojung Lee, Jungwoo Kang, Minchul Cho, Eunhee Seo, Heesook Choi, Eunjin Kim, Junghee Kim, Heejong Kim, Gum Yong Kang, Kwang Pyo Kim, Young-Ho Park, Dae-Yeul Yu, Young Na Yum, Sue-Nie Park, Do-Young Yoon
• Journal: International journal of oncology (Int J Oncol) Vol. 34 Issue 1 Pg. 161-72 (Jan 2009) ISSN: 1019-6439 [Print] Greece
• PMID: 19082487 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor

Topics

• Adenoma (genetics, metabolism, pathology)
• Animals
• Biomarkers, Tumor (genetics, metabolism)
• Electrophoresis, Gel, Two-Dimensional
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Genes, ras (physiology)
• Humans
• Lung Neoplasms (genetics, metabolism, pathology)
• Mice
• Mice, Transgenic
• Oligonucleotide Array Sequence Analysis
• Proteomics (methods)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Transcription, Genetic